The zebrafish is now a common, non-mammalian model of human disease due to experimental features such as small size, transparency, and powerful genetic tools. In response to NIH-sponsored Zebrafish and Aquatic Models working groups' recommendations, an important piece of American scientific infrastructure is being established in the form of a web-based atlas of anatomy, histology, and pathology. This atlas will be accessible from www.zfatlas.psu.edu and the Zebrafish Information Network (ZFIN) at the University of Oregon (www.zfin.org). Normal anatomy will serve as critical context for the study of abnormal anatomy caused by genetic deficiencies and disease. The atlas' personnel, imaging and computer hardware and web site comprise the infrastructure for users to view mutant/morphant/diseased zebrafish in the context of normal, in both 2D and 3D. Specific Aim 1 is to integrate abnormal phenotypes into the atlas starting with an established mutant collection, to create a nondestructive mechanism for remote labeling of web-based, state-of-the-art virtual slides that allows viewing of histological tissue sections at different powers, to integrate the zebrafish atlas with other web-based resources including the home of zebrafish web-based resources (www.zfin.org), and to use the web interface to display a range of mutant phenotypes. Specific Aim 2 is to develop mechanisms for analyzing and displaying 3D zebrafish data. We will segment and label different organs from digital 3D representations of zebrafish, and explore, test, and implement integrated interfaces between virtual slides and 3D representations of zebrafish created by microCT imaging at subcellular resolutions. Specific Aim 3 is to build a foundation for structural and functional integration across models systems. This aim will utilize zebrafish, mouse, and human as the organisms of interest, and use specific skeletal, eye, and skin color mutations as a paradigm for describing the roles of model systems in understanding a biological function and disease. This aim will focus on normal tissues shared by all three species followed by pathology shared by all three species. The integrations of this community resource will serve as a model for all model system web sites, serving multiple missions across the NIH. PUBLIC HEALTH RELEVANCE (provided by applicant): Compelling experimental features have made the zebrafish a model for a wide range of human maladies, including cancer, heart disease, and infection. The atlas (www.zfatlas.psu.edu) contains high-resolution 2D and 3D representations of normal and, as proposed, abnormal zebrafish. By cross-referencing with other model systems, the atlas will also provide infrastructure for integrative, multidisciplinary projects.